Cancer is a group of diseases characterized by aberrant control of cell growth. The annual incidence of cancer is estimated to be in excess of 1.3 million in the United States alone. While surgery, radiation, chemotherapy, and hormones are used to treat cancer, it remains the second leading cause of death in the U.S. It is estimated that over 560,000 Americans will die from cancer each year.
Cancer cells simultaneously activate several pathways that positively and negatively regulate cell growth and cell death. This trait suggests that the modulation of cell death and survival signals could provide new strategies for improving the efficacy of current chemotherapeutic treatments.
Breast cancer is generally treated with a combination of surgery to remove the cancerous lesion and adjuvant therapy—radiation, chemotherapy or both—to attack any cancer cells that may be left after the surgery. Breast cancer can be classified broadly by the presence or absence of hormone receptors (HRs). Hormone receptor positive (HR+) cancer is characterized by the expression of one or both female hormone receptors—estrogen receptor (ER) or progesterone receptor (PR). Adjuvant therapy for ER+ breast cancer often includes chemotherapy with a selective estrogen receptor modulator (SERM), such as tamoxifen or raloxifene. Unfortunately, while about 70% of breast cancers are ER positive, the remaining 30% of breast cancers that are HR negative are not amenable to treatment with SERMs. Accordingly, other adjuvant chemotherapies, such as treatment with an anthracycline (alone or in combination with a taxane) have been tried on ER negative breast cancer.
Treatment with anthracycline is limited by lifetime dosing limits based on cardiotoxicity concerns. Treatment with gemcitabine and carboplatin is an established combination chemotherapy for metastatic breast cancer patients—whether taxane-naïve or taxane-pretreated. Platinum agents have demonstrated promising antitumor activity in basal-like locally advanced breast cancers. DNA damaging agents have promising antitumor efficacy against basal-like breast cancer because of defects in DNA repair pathways inherent in these breast cancers.
Despite the availability of antimetabolites such as gemcitabine and platinum complex agents such as carboplatin, there is no accepted standard of care for ER negative breast cancer. In particular, triple negative metastatic breast cancer (i.e. breast cancer that is ER negative, and/or PR negative, and/or human epidermal growth factor receptor 2 (HER2) negative) is refractory to standard treatments and is entirely refractory to SERM chemotherapy. There is thus a need for an effective treatment for cancer in general, and especially for triple negative metastatic breast cancer.
Although there are limited therapeutic options for cancer treatment, variants of cancers, including triple negative breast cancer, are especially difficult because they can be refractory to standard chemotherapeutic or hormonal treatment. There is thus a need for an effective treatment for cancer in general, and cancer variants in particular.